alveolar rhabdomyosarcoma

Images

 Alveolar rhabdomyosarcoma.

• https://twitter.com/histiocytosisX/status/699599913013923840
• https://twitter.com/seattlequinns/status/855202143564742656

 ARMS : focal desmin w/ diffuse myogenin in A-RMS (PCR + PAX3-FOXO1)

• https://twitter.com/histiocytosisX/status/730475540524699649

 Compact ARMS : Alveolar rhabdomyosarcoma may lack alveolar spaces. Solid nodules uniform round cells,fibrous septa. DIFFUSE myogenin.

• https://twitter.com/JMGardnerMD/status/856870953011347456

Digital slides

 Case 220 (HPC:220) : Alveolar rhabdomyosarcoma
 Case 215 (HPC:215) : Alveolar rhabdomyosarcoma, solid variant
 UI:879 - Alveolar rhabdomyosarcoma

Localization

 limbs
 orbit
 perineal region
 lungs
 skin (12131163)

Complications

 disseminated intravascular coagulation (DIVC)
 hyperfibrinolysis

Variants

 solid alveolar rhabdomyosarcoma (compact alveolar rhabdomyosarcoma) (8172322, 11280599)
 embryonal-like alveolar rhabdomyosarcoma with PAX3 rearrangement at 2q35 by t(2;20)(q35;p12) (15120913)
 multiple morphological alveolar rhabdomyosarcomas (17097083)

Cytogenetics and molecular biology

Cytogenetic and molecular studies have shown that approximately 80% of cases of alveolar rhabdomyosarcoma (ARMS) have consistent chromosomal translocation of either t(2;13) or t(1;13), resulting in either PAX3-FKHR or PAX7-FKHR gene fusions. However, 20% of the cases diagnosed histologically are negative for these fusion genes. The expression of PAX3-FOXO1A and PAX7-FOXO1A identifies a very high-risk subgroup (12039929)

 PAX3 rearrangements at 2q35 (PAX3 fusion genes)

• FOXO1A-PAX3 by t(2;13)(q35;q14) (55%) (12039929, 12550764)
• NCOA1-PAX3 fusion gene by t(2;2)(q35;p23) (PAX3 at 2q35 and NCOA1 at 2p23) (15313887)
• PAX3-X unknown gene by t(2;20)(q35;p12) (PAX3 at 2q35 and unknown gene at 20p12) (15120913)

 PAX7 rearrangements at 1p36 (PAX7 fusion genes)

• PAX7/FOXO1A fusion gene by t(1;13)(p36;q14) (PAX7 at 1p36 and FOXO1A at 13q14) (22%) (12039929)
• t(1;16)

 no fusion transcript detected in 20% of the cases (12183429, 12039929)

 other translocations decribed

• t(6;11)(q27;q13) (17097083)

 secondary translocations

• t(1;16)(q21;q13) (11%) (8625268)

Regional amplification

 2p24 amplification (MYCN amplification) (9872655, 11063797)
 13q31 amplification (10825007)
 12q13-15 amplification

• MDM2 amplification (8751388, 10918230, 8946207)
• CDK4 amplification (8946207)

 amplification of the fusion genes

• PAX7-FKHR fusion gene (11063797)

Deletions

 CDKN2A/B in 9q21

Other chromosomal anomalies

 hypotetraploidy (10825007)
 isochromosome 1q (9809033)

Expression profiling: 9823299

CESH

 Nascent pre-rRNA overexpression correlates with an adverse prognosis in alveolar rhabdomyosarcoma (16770781)

Links

 AGCOH

See also

 rhabdomyosarcomas (RMSs)

• embryonal rhabdomyosarcoma (ERMS)
• alveolar rhabdomyosarcoma
• sclerosing rhabdomyosarcoma (SRMS)
• pleomorphic rhabdomysoarcoma (PRMS)

Reviews

 Mercado GE, Barr FG. Fusions involving PAX and FOX genes in the molecular pathogenesis of alveolar rhabdomyosarcoma: recent advances. Curr Mol Med. 2007 Feb;7(1):47-61. PMID: 17311532

 Barr FG. Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma. Oncogene. 2001 Sep 10;20(40):5736-46. PMID: 11607823

References

 Parham DM, Qualman SJ, Teot L, Barr FG, Morotti R, Sorensen PH, Triche TJ, Meyer WH; Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children’s Oncology Group. Am J Surg Pathol. 2007 Jun;31(6):895-901. PMID: 17527077

 Williamson D, Lu YJ, Fang C, Pritchard-Jones K, Shipley J. Nascent pre-rRNA overexpression correlates with an adverse prognosis in alveolar rhabdomyosarcoma. Genes Chromosomes Cancer. 2006 Sep;45(9):839-45. PMID: 16770781

 Sorensen PH, Lynch JC, Qualman SJ, Tirabosco R, Lim JF, Maurer HM, Bridge JA, Crist WM, Triche TJ, Barr FG. PAX3-FKHR and PAX7-FKHR gene fusions are prognostic indicators in alveolar rhabdomyosarcoma: a report from the children’s oncology group. J Clin Oncol. 2002 Jun 1;20(11):2672-9. PMID: 12039929

 Taylor AC, Shu L, Danks MK, Poquette CA, Shetty S, Thayer MJ, Houghton PJ, Harris LC. P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines. Med Pediatr Oncol. 2000 Aug;35(2):96-103. PMID: 10918230

 Khan J, Simon R, Bittner M, Chen Y, Leighton SB, Pohida T, Smith PD, Jiang Y, Gooden GC, Trent JM, Meltzer PS. Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. Cancer Res. 1998 Nov 15;58(22):5009-13. PMID: 9823299

 Berner JM, Forus A, Elkahloun A, Meltzer PS, Fodstad O, Myklebost O. Separate amplified regions encompassing CDK4 and MDM2 in human sarcomas. Genes Chromosomes Cancer. 1996 Dec;17(4):254-9. PMID: 8946207